There are major gaps in knowledge regarding the etiologic mechanisms, psychosocial effects, natural history, and medical and psychosocial management of women with disorders of the hypothalamic-pituitary-ovarian axis. An international research consortium and disease registry formed under the guidance of an umbrella organization would provide a pathway to comprehensively increase basic and clinical knowledge about these conditions. Such a consortium and patient registry also would provide clinical samples and clinical data with a goal toward defining the specific pathogenic mechanisms. An international collaborative approach that combines the structure of a patient registry with the principles of integrative care and community-based participatory research is needed to advance the field of primary ovarian insufficiency. The program is in the early phases of organizing such an international effort using primary ovarian insufficiency as the focus. We reported this year that hormone replacement therapy restore bone mineral density to normal in young women with primary ovarian insufficiency (POI). The findings provide important treatment information for women with POI and their physicians. Spontaneous POI affects 1 in 100 women by age 40. With no apparent cause, the ovaries of affected women dont work normally. They stop regularly releasing eggs and produce low levels of reproductive hormones, including estradiol (a type of estrogen) and testosterone (a predominantly male hormone that is also produced by women in smaller amounts). Women with POI have hot flashes, fertility problems, and irregular or no menstrual cycles. They also have reduced bone mineral density, which can lead to osteoporosis and bone fractures. Hormone replacement therapy regimens have been well studied and optimized to improve bone health in postmenopausal women. But there has been limited research on the effects of these therapies in younger women. A team led by Drs. Vaishali B. Popat and Lawrence M. Nelson of NIHs Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) tested the effects of hormone replacement therapy on bone health in young women with POI. The trial was done at NIHs Clinical Center in Bethesda, Maryland. The team enrolled 145 women with POI between the ages of 18 and 42. The women were randomly assigned to 2 groups. One received an estradiol patch, progestin pills, and a testosterone patch. The other received an estradiol patch, progestin pills, and an inactive placebo patch. The researchers used bone density scans of the hip and lower spine to measure the effects of the regimens. For comparison, the scientists also measured bone mineral density in an untreated group of 70 women with normal ovarian function. Results were published online on June 6, 2014, in the Journal of Clinical Endocrinology & Metabolism. Both hormone treatment regimens led to increases in bone mineral density at 3 years. When the study began, women with POI had significantly lower hip and spine bone mineral density levels than those in the control group. By the studys end, bone density measures in both treatment groups had increased to the same level as the women without POI. The group receiving a testosterone patch didnt gain further benefits over those with a placebo patch. Studies with a greater number of women would be needed to learn whether testosterone replacement might benefit women with POI, the researchers note. While hormone replacement therapys effect on bone mineral density has been studied in postmenopausal women, there is limited research on the effects of this therapy in younger women. This study showed that not only could hormone treatment reduce the rate at which women with POI lose bone mineral density, but it could actually restore bone density to normal levels. Since women with primary ovarian insufficiency (POI) display low androgen levels, which could contribute to mood and behavioral symptoms observed in this condition. We examined the effects of physiologic testosterone therapy added to standard estrogen/progestin therapy on quality of life, self-esteem, and mood in women with POI. One hundred twenty-eight women with 46,XX spontaneous POI participated in a 12-month randomized, placebo-controlled, parallel-design investigation of the efficacy of testosterone augmentation of estrogen/progestin therapy. Quality of life, self-esteem, and mood symptoms were evaluated with standardized rating scales and a structured clinical interview. Differences in outcome measures between the testosterone and placebo treatments were analyzed by Wilcoxon rank sum tests. No differences in baseline characteristics, including serum hormone levels (P > 0.05), were found. Baseline mean (SD) Center for Epidemiologic Studies Depression Scale scores were 10.7 (8.6) and 9.2 (7.8) for testosterone and placebo, respectively (P = 0.35). After 12 months of treatment, measures of quality of life, self-esteem, and mood symptoms did not differ between treatment groups. Serum testosterone levels achieved physiologic levels in the testosterone group and were significantly higher compared with placebo (P < 0.001). Baseline testosterone levels were not associated with either adverse or beneficial clinical effects. We conclude that a 150-&#956;g testosterone patch achieves physiologic hormone levels in women with POI. Our findings suggest that augmentation of standard estrogen/progestin therapy with physiologic testosterone therapy in young women with POI neither aggravates nor improves baseline reports of quality of life or self-esteem and had minimal effects on mood. Other mechanisms might play a role in the altered mood accompanying this disorder.